23
month, then such small amounts of transport should bemade available, either to Civil Affairs or to UNRRA. Wesuspect that such matters are overlooked or postponedjust because they are so small, and that a man thinkingin terms of shells for an army is not likely to see therelative- importance of a package of insulin. Moreover,the objectives of Civil Affairs and UNRRA are not identical.The primary aim of Civil Affairs is to prevent civilianproblems from hampering the armies : the primary aimof UNRRA is to provide relief. Now that the armiesare handing over to the French Government completecontrol of the zone intérieure of France, it should be
possible for UNRRA to begin its own work of relief even ona small scale. But it must be given the small butessential transport facilities required.
PREGNANCY TESTS
THERE are now three tests for pregnancy which dependon the demonstration of an increased quantity of chori-onic gonadotrophin in the urine. It is hard to knowwhat names to use for them. Reference to the animal
employed may lead to confusion-the " mouse " test, sounds all right, but the " rabbit " test is often mis-heard as- the " rapid " test, and as- for the third, theanimal is strictly speaking neither frog nor toad, and" xenopus" sounds rather pompous. The use of
epqnyms is the commoner practice, though the namesAschheim, Friedman, and Hogben are frequently mis-spelt.The Aschheim-Zondek test has already proved its
reliability, and for many years Professor Crew was ableto report a very low percentage of error with it from theEdinburgh Pregnancy Diagnosis Station. Almost everystep in the procedure, from the preliminary weighingof the mice to the diurnal injections, the gassing, and thedissection and mounting of the ovaries, can be left tothe trained technician, and only the inspection andreading of the ovaries need be undertaken by the directorof the station. A big colony of mice, or a reliable
supplier, is essential. By using 5 mice for each test, theoccasional refractory animal is virtually eliminated, andfalse positives should be rare provided the weight, andtherefore the age, of the mice has been carefully checked.The great disadvantage of this test is that it takes 5
days to perform.The Friedman test, which is now almost as well known,
is perhaps more suited to the smaller laboratory than tothe pregnancy diagnosis station. Small numbers of doerabbits need to be kept in stock and each strictly segre-gated not only from bucks but from other does. Theintravenous injection of the untreated, or simply filtered,urine demands some technical skill which is acquired bypractice. Results may be read in 48 hours. The testanimal can be eliminated as a possible source of error.A preliminary laparotomy will allow inspection of theovaries before the test is begun ; 48 hours after injectionof the urine for diagnosis another laparotomy may revealthe characteristic corpora lutea and hæmorrhagica of apositive test, or it may reveal no change in the appear-ance of the ovaries. Injection of a known urine of
pregnancy will now make sure that the-individual rabbitwill respond to chorionic gonadotrophin, and that theappearances found after the second laparotomy werethose of a true negative test. This procedure, whilebestowing on the test a high degree of accuracy, rendersit unsuitable for use on a large scale.The Hogben test has the great advantage of speed,
and only those familiar with pregnancy diagnosis testswill appreciate how important that is. A woman,
. content to have missed her period by many days, willsuddenly decide that she must know at once whethershe is pregnant or not. Xenopus will give her theanswer within a day. For some years difficulty wasexperienced in this country with the Hogben testbecause it was impossible to breed the animals. This
difficulty has now been overcome. There is neverthelessone serious disadvantage to the test-if untreated urineor alcohol-precipitated extract is injected, it kills 15%or more of the animals. Preparation of the urine tomake it less lethal is an elaborate process depending onthe adsorption of the gonadotrophin on kaolin, but in apregnancy diagnosis station this can of course be carriedout on a a large scale without seriously inconveniencingthe organisation. It is advisable to kill animals not
showing extrusion of ova overnight, for in some casesova are found in the oviducts on post-mortem examina-tion and an apparently negative test may prover to bepositive. ’
From each of’ these three standard tests an accuracyof about 98-5% may be obtained provided a detailedtechnique is developed in the hands of experiencedworkers. The Friedman test is suited to the small
laboratory with a qualified research-worker who willconduct most of the steps of the tests himself. TheAschheim-Zondek and Hogben tests are more suitedto the pregnancy diagnosis station, where such manipula-tions as multiple- injections of animals and chemicalpreparation of the urine can be placed in the hands oftrained technicians, the reading of results being aloneleft to a qualified director. Under such conditionsminor variations in technique assume less importance.
NUCLEAR TISSUE
THE basis of practically all histology is the use ofstains which distinguish the nucleus from the cytoplasm.By this device the minute structure of the whole bodyhas been made out, and the sequence of changes whichthe nucleus undergoes in cell division has been observed.These are matters of common knowledge to most of us,however long ago we may have taken our final MB, butwithin the last 25 years the irrepressible biochemistshave greatly disturbed this quiet little medical back-water. Their achievements, recently reviewed byDavidson and Waymouth,1 now constitute an importantdevelopment in medical science.The nucleotides are the basis of all nuclear structure
and there are, broadly speaking, two kinds. Both con-tain a purine or pyrimidine base, a carbohydrate anda phosphoric acid group, but they differ in that in onethe carbohydrate is desoxyribose and in the otherribose. This apparently minor structural change confers
considerable functional differences on the nucleotides.Those containing desoxyribose condense into moleculeswith molecular weights of upwards of 1,000,000, and arecharacteristically found in the nuclei of cells. Theothers condense less readily and are found mostly in thenucleolus, the cytoplasm, in cells without visible nuclei,and in viruses. Nucleotides containing ribose andadenine act as co-enzymes in cell respiration, and it is
interesting to recall that two of the B vitamins-ribo-flavin and nicotinic acid-also enter into the compositionof these enzyme systems.
Ribose nucleotides are broken down by an enzymewhich has now been isolated and crystallised. Thisenzyme is heat-stable-i.e., it is not destroyed at100 ° C-and it has been prepared and utilised to differ-entiate the two kinds of nuclear material in cells.Within the last 8 years a method of " staining " nuclearmaterial has been introduced by Caspersson of Stock-holm. The purine and pyrimidine bases absorb ultra-violet light much more intensely than any other cellconstituents, and by using this light and photographingthe cells through quartz lenses the distribution of nuclearmaterial and alterations in its concentration can be.followed. Both these techniques have contributedgreatly to our recent knowledge, but there are othercontributors, one of them being the ultracentrifuge.By this instrument macromolecular complexes can be
1. Davidson, J. N., Waymouth, C. Nutr. Abstr. Rev. 1944, 14, 1.
24
isolated. The nucleic acids form just such complexeswith other cell constituents, and proteins and phos-pholipins have been identified in them. Some of theinfective agents, such as the virus of the Rous sarcoma,have been shown to contain these phospholipin com-plexes, but they are not confined to such material andwere first isolated from embryonic tissue. Methods of
separating the nuclei from the cytoplasm by mechanicalmeans have also been devised, and these enable thenuclei to be subjected to analysis, not only for proteinsand nucleic acids, but also for minerals.2 The structureof the nucleoproteins is analogous to that of some of theoxidising enzymes, and it is tempting to picture themacting in some such capacity in the cell. They are,however, characteristically associated with self-repro-ducing systems or agents such as genes and viruses, andit is in conferring this property upon a tissue that theyappear to exert their major role. It has been suggestedthat the ribonucleic acids enable the cytoplasm to growand reproduce itself.One of the problems still to be solved is the metabolic
relationship of the ribo- to the desoxyribo-nucleic acids.Mitchell, working at Cambridge, believes that ribo-nucleotides accumulate in the plasma of rapidly growingcells, and that these are then changed into desoxyribo-nucleic acid and deposited in the nuclei, which,reproducethemselves at cell division. This is an interestingsuggestion, but the conversion involves the reduction ofthe ribose and the methylation of a pyrimidine base.;Neither of these reactions has been shown to occur invivo, but both are inherently possible: This mustawait further investigation, but meanwhile knowledgeof fundamentals is rapidly accumulating, and with anyluck some of it will be of direct value to therapeutics.
BRACHIAL NEURITIS OR HERNIATED DISC?
UNTIL about ten years ago it was generally believedthat sciatica was due to sciatic neuritis or radiculitis,a form of interstitial neuritis almost equally familiar inthe upper limb as brachial neuritis. Now most expertsagree that sciatica is usually caused by a herniatedintervertebral disc, and it is not surprising that thisdiscovery should have aroused fresh interest in brachialneuritis. Is that long-accepted diagnosis based upon anequally insecure pathology ? On another page MajorElliott and Major Kremer report 8 cases of brachialpain which they attribute to herniatiori rof a cervicalintervertebral disc. They describe a fairly clear-cutclinical picture which hitherto would probably have beenlabelled brachial neuritis. But it appears to be moredifficult to establish the presence of a herniated inter-vertebral disc in the cervical than in the lumbar region.In Elliott and Kremer’s cases the composition of thecerebrospinal fluid was normal and Queckenstedt’s testyielded no evidence of spinal block. The X-ray changesdescribed appear for the most part to be those of spinalspondylitis, which may or may not be associated witha herniated disc, or may even produce similar symptoms.Myelography with ’ Pantopaque,’ when this is generallyavailable, may make the diagnosis more certain, as inthe 3 cases of this series in which it was used. Elliottand Kremer’s work will help towards the recognition ofone cause of brachialgia and so indirectly clarify thediagnosis of other causes.
Experience with herniated lumbar discs has shownthat it takes a considerable time to assess the results ofvarious methods of treatment and arrive at a suitableroutine. Elliott and Kremer are wisely conservative.Immobilisation, either by rest or by a plaster jacket,has proved its worth in the treatment of lumbar hernia-tions, and the same principle seems applicable to the farmore mobile neck. Paradoxically, manipulation mayalso be effective. While theoretically this procedure2. Williamson, M. B., Gulick, A. J. cell. comp. Physiol. 1942, 20, 116.
involves a risk of producing compression of the cervicalspinal cord, the risk must be very slight, for manypatients with " brachial neuritis " have had their necksmanipulated without disaster and sometimes withbenefit. The indications for surgery have yet to bedetermined : Elliott and Kremer did not think it
necessary for many of their patients, and we mustremember that most patients recovered from sciaticaand brachial neuritis before a surgical cause was suspectedfor either, and that the mortality-rate of both is lowerthan that of laminectomy for herniated disc.
STRESS FRACTURES OF THE FIRST RIB
IN examining ,55,451 routine chest radiograms inRoyal Naval personnel, Alderson has discovered anunexpected anomaly of the first rib in 35 cases. Thesite of the lesion was constantly just proximal to thescalene tubercle and the appearance varied from an
irregular break, transverse or oblique, partial or complete,to a fusiform swelling of callus or of solid bone. All the
subjects were males, no cases being found among the3433 women examined, and the incidence was highest inthe 15-20 age-group ; 30 of the 35 were men under25. Only 5 had significant clinical features or history-2 complained of sudden pain in the shoulder after
physical training, 2 recalled local trauma in previousyears, and 1 had been carrying heavy weights on thatshoulder just before enlistment. In 2 cases serialobservation of the repair process showed the early breakand later development of callus and bone, with regressionof the lesion ; and in one a temporary opacity of thelung apex medial to the fracture was originally regardedas tuberculous.
Alderson regards the lesion as a stress fractureessentially similar to those reviewed by Hartley 2 in themetatarsals, calcaneus, tibia, fibula, femur, pubis, andvertebrae; but while these are due to the effects of
body-weight, the present lesion is more analogous tofractures of the humerus from chronic overuse. Theanatomical facts support this view. The scalenusanterior and medius are inserted into the rib on eachside of the subclavian groove, and if these musclessuddenly contract the subclavian artery and lower trunkof the plexus act as a restraining strap holding down theintervening portion of rib at the point where fractureoccurs. In this mechanism the first digitation of theserratus anterior and the subclavius may play somepart. While fractures of ribs by muscular violence arenot rare, the first rib is only uncommonly involved.But this lesion seems likely to be a gradual yieldingof march fracture type-certainly not a congenitalanomaly, for the line of fusion of primary and secondaryossification centres is well posterior. The frequency inyouth and the fact that most of the cases were in menstraight from strenuous physical training also fit with anorigin in muscular violence.
THE COMPLETE BLOOD SUBSTITUTE
THE discovery in Sweden has been announced of anic artificial blood plasma, capable of use by injection in
’
the same way a& real blood transfusion." 3 So far, noprecise information has reached this country concerningthis contribution to the transfusion problem. No moreis known than the broad announcement that the sfib-stitute is a derivative of " sugar," named
" dextran,"which can be produced in unlimited quantities in powderform, while the reconstituted fluid can be sterilised byboiling. These features are of course necessary functionsof the complete blood substitute, but it will be clear, evenfrom the scanty facts available, that one or more ofother properties, equally fundamental, are likely to bemissing. The ideal blood substitute must have oxygen-
1. Alderson, B. R. Brit. J. Radiol. 1944, 17, 323.2. Hartley, J. B. Ibid, 1943, 16, 255, 348.3. Times, Dec. 8, 1944.